Oxygen-regulated post-translation modifications as master signalling pathway in cells

Oxygen is essential for viability in mammalian organisms. However, cells are often exposed to changes in oxygen availability, due to either increased demand or reduced oxygen supply, herein called hypoxia. To be able to survive and/or adapt to hypoxia, cells activate a variety of signalling cascades resulting in changes to chromatin, gene expression, metabolism and viability. Cellular signalling is often mediated via post-translational modifications (PTMs), and this is no different in response to hypoxia. Many enzymes require oxygen for their activity and oxygen can directly influence several PTMS. Here, we review the direct impact of changes in oxygen availability on PTMs such as proline, asparagine, histidine and lysine hydroxylation, lysine and arginine methylation and cysteine dioxygenation, with a focus on mammalian systems. In addition, indirect hypoxia-dependent effects on phosphorylation, ubiquitination and sumoylation will also be discussed. Direct and indirect oxygen-regulated changes to PTMs are coordinated to achieve the cell's ultimate response to hypoxia. However, specific oxygen sensitivity and the functional relevance of some of the identified PTMs still require significant research. Cellular signalling is often mediated via post-translational modifications, also in response to hypoxia. This review discusses the impact of changes in oxygen availability to PTMs and how such oxygen-regulated changes are coordinated to achieve cellular responses to hypoxia.image

Automated summary

Oxygen is crucial for mammalian organisms' viability, and cells activate various signaling cascades to survive and adapt to changes in oxygen availability. These cascades lead to alterations in chromatin, gene expression, metabolism, and viability, which are often mediated by post-translational modifications (PTMs). The direct impact of changes in oxygen availability on PTMs, such as proline, asparagine, histidine, and lysine hydroxylation, lysine and arginine methylation, and cysteine dioxygenation, is reviewed in this article, with a focus on mammalian systems. Additionally, indirect effects on phosphorylation, ubiquitination, and sumoylation in response to hypoxia are discussed. The coordination of direct and indirect oxygen-regulated changes to PTMs is critical for the cell's response to hypoxia, but further research is needed to understand the specific oxygen sensitivity and functional relevance of certain PTMs.